1. Field of the Invention
This invention relates to a monoclonal antibody specific to active human ceruloplasmin, a method for detecting or quantifying human ceruloplasmin using the same, and to a method for diagnosing Wilson's disease using the same.
2. Description of the Related Art
Ceruloplasmin is a kind of plasma protein, which is found in the .alpha..sub.2 macroglobulin fraction. It is a copper-containing glycoprotein, the level of which in normal human serum is 20-50 mg/dl. Therefore, it plays an important role in the metabolism of copper. The ceruloplasmin level in serum of a patient suffering from Wilson's disease, or an infectious disease, or of a pregnant woman is different from that of a normal human, so that quantification of human ceruloplasmin may be used for the diagnosis of these diseases and pregnancy.
Wilson's disease is caused by a decrease in ceruloplasmin activity and presents brain and liver disorders. Although it used to be believed that this disease is caused by a decrease in the amount of ceruloplasmin per se, recently, it was shown that this disease is caused by inactive ceruloplasmin (i.e., sharp decrease in active ceruloplasmin) (36th Japan Human Genetics Society, October, 1991). Thus, a method for directly or indirectly measuring inactive or active human ceruloplasmin is desired. Wilson's disease is one of the rare diseases which is curable by using a chelating agent if the disease is found when the patient is an infant, so that it is desired to detect this disease when the patient is an infant. However, ceruloplasmin activity is intrinsically low in infancy, so that it is difficult to detect Wilson's disease in infants.
It has been proposed to measure ceruloplasmin by measuring the peroxidase activity of ceruloplasmin (Schosinsky et al., Clin. Chem., 201, 1974). However, since there is no substrate which is specific to ceruloplasmin alone, it is impossible to specifically quantify ceruloplasmin alone by peroxidase activity. Further, since this method has low sensitivity, it is impossible to distinguish a Wilson's disease patient from a normal person when the patient is an infant.
It has also been proposed to measure human ceruloplasmin by using a polyclonal antibody specific to human ceruloplasmin (Nippon Rinsho, Vol. 47, Extra Number, p.758, 1989). However, polyclonal antibody specifically reacts with not only active ceruloplasmin but also with inactive ceruloplasmin; thus, it is difficult to distinguish a Wilson's disease patient from a normal person. A monoclonal antibody specific to human ceruloplasmin has also been reported (Biokhimiya, Vol. 55, No. 2, 361-367 (1990)). However, since this monoclonal antibody also reacts with both active and inactive human ceruloplasmin, this monoclonal antibody also cannot be used for the detection of Wilson's disease.